A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERIIMPLANT DISEASES
¹Dental Department, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
aBDS, AEGD, SSC-ARD, SF-DI, Consultant in Cosmetic Restorative and Implant Dentistry
Received: February 01, 2017
Revised: February 23, 2017
Accepted: March 06, 2017
Published: March 07, 2017
Academic Editor: Constantinus Politis, MD, DDS, MM, MHA, PhD, Professor and Chairperson, Department of Oral and Maxillofacial Surgery Faculty of Medicine University of Leuven, Leuven, Belgium
Cite this article:
Alshehri M. A comprehensive review of systemic factors associated with periimplant diseases. Stoma Edu J. 2017;4(1):39-45.
Dr Mohammed Alshehri, BDS, AEGD, SSC-ARD, SF-DI, Dental Department, King Khalid, University Hospital, King Saud University, Riyadh, Saudi Arabia.
Tel/Fax: +96.655.380.333 / +966.114.672.428, e-mail: firstname.lastname@example.org
Background: A variety of systemic factors have been associated with peri-implant diseases. Objective: The aim of the present comprehensive review was to assess current literature regarding the systemic factors associated with the etiology of peri-implant diseases.
Results: Both normal and premalignant oral mucosa cells (NOK and POE9i) displayed uptake of PLGAChiNPs in a time and concentration-dependent manner, both in 2D and 3D models. A higher and more rapid uptake of PLGAChi NPs by precancerous cell line POE9i was observed when compared to NOKs. Interestingly, DPCs did not display internalized PLGAChi NPs, even at the highest concentration of 200 g/mL.
Data source: Databases were searched till January 2017 using different combinations of the following key words: “acquired immune deficiency syndrome”; “cancer”; “diabetes mellitus”; “genetic”; “peri-implant diseases”; “peri-implantitis”, “renal”; and “risk-factors”.
Study selection: Clinical studies assessing the systemic factors associated with the etiology of peri-implantitis were included. Letters to the Editor, case-reports, case-series, in-vitro studies, studies on animal models and commentaries were excluded.
Data extraction: The pattern of the present comprehensive review was customized to primarily summarize the pertinent information.
Data synthesis: Poorly-controlled diabetes mellitus (DM) is a significant risk factor for peri-implant diseases; however, under optimal glycemic control dental implants can osseointegrate in patients with DM. Osteoporosis and rheumatoid arthritis have been associated with peri-implant diseases; however, implant surface modifications and optimal oral hygiene maintenance are essential parameters that can facilitate osseointegration in these patients. Although irradiation is a significant risk-factor for peri-implant diseases; studies have shown that osseointegration and survival of implants is possible in cancer patients. There is a weak evidence that HIV infection is no more a contradiction for implant therapy. Although systemic diseases are significant risk-factors for dental implant failure, proper management of the systemic disorder and optimal oral hygiene may support osseointegration and survival of dental implants in medically-compromised patients.
Keywords: acquired immune deficiency syndrome, cancer, diabetes mellitus, genetic, peri-implant diseases.
Although studies1-3 have reported implant success and survival rates of up to 100%; a number of systemic factors have been reported to jeopardize the success and survival of dental implants.4, 5 According to a consensus report from the 6th European Workshop on Periodontology, peri-implantitis is defined as the presence of inflammation of the peri-implant mucosa and concurrent loss of supporting alveolar bone.6 Mombelli et al.7 described peri-implantitis as a site-specific inflammatory condition, which displays clinical and radiographic features that are similar to those in patients with chronic periodontitis. Data regarding the prevalence of peri-implantitis is inconsistent. In the study by Koldsland et al.,8 the prevalence of peri-implantitis ranged between 11.3% and 47.1%; whereas Mombelli et al.9 reported peri-implantitis in 20% of their study population during 5 to 10 years of follow-up. In the study by Zitzmann and Berglundh,6 the frequency of peri-implantitis varied between 28% and at least 56% of the participants and 12% and 43% of individual implants. Peri-implant diseases are categorized into two types namely, peri-implant mucositis and peri-implantitis. Peri-implant mucositis is characterized by inflammation of soft tissues around the implant without any signs of peri-implant alveolar bone loss.6 Patients with peri-implant mucositis exhibit bleeding on probing (BOP), peri-implant probing depth ≥ 4mm and/or suppuration.10,11
A variety of factors, local as well as systemic factors have been associated with the etiology of peri-implantitis.12-16 It is well known that poor oral hygiene, tobacco smoking, poor bone quality and quantity, jaw location and bruxism are among the most common local factors associated with the etiology of peri-implantitis. Nevertheless, the contribution of systemic factors such as immunosuppression (as observed in patients with acquired immune deficiency syndrome, osteoporosis, poorly-controlled diabetes mellitus and cancer) and use of medications (such as bisphosphonates and corticosteroids) that have also been associated with the etiology of peri-implantitis cannot be disregarded (Fig. 1).17-21 Considering the length of the article, the author dedicated the present article to comprehensively review the systemic risk-factors associated with the etiology of peri-implantitis. The aim of the present comprehensive review was to provide an overview of current literature regarding the systemic conditions associated with the etiology of peri-implantitis.
2. Materials and methods
2.1. Focused question
The addressed focused question was “Which systemic conditions are associated with the etiology of peri-implant diseases?”
2.2. Literature search strategy
PubMed/Medline, Scopus, EMBASE, ISI Web of knowledge and Google-Scholar databases were searched from till January 2017 using the following key words: “arthritis”, “cancer”, “diabetes mellitus”; “acquired immune deficiency syndrome”; “renal disorders”; “osteoporosis”, “peri-implant/ periimplant” and “genetics”.
Clinical studies assessing the local risk-factors associated with the etiology of peri-implant diseases were included.
2.3. Eligibility criteria
Results from only clinical studies were included. Letters to the Editor, historic reviews, case-reports, case-series, in-vitro studies, studies on animal models and commentaries were excluded. The pattern of the present comprehensive review was customized to primarily summarize the pertinent information.
3.1. Diabetes mellitus
Diabetes mellitus (or diabetes) is a common metabolic disorder characterized by hypergly-cemia due to impaired insulin secretion, insufficient insulin action, or both.22 The main types of diabetes include type 1 diabetes and type 2 diabetes. Type 1 diabetes is associated with pancreatic beta (β)-cell destruction and accounts for 5-10% of the subjects with diabetes.
Type 2 diabetes is associated with a relative, rather than an absolute insulin deficiency and accounts for 90-95% of all individuals with diabetes.23 Individuals with poorly-controlled diabetes are more susceptible to develop complications after implant therapy compared to individuals with well-controlled diabetes.24
Chronic hyperglycemia has been related with tissue damage, since endothelial cells take up glucose passively in an insulin-independent manner.25,26 Hyperglycemia is also associated with an altered host resistance, for example, defective migration of polymorphonuclear leukocytes, impaired phagocytosis and an exaggerated inflammatory response to microbial products.27
The treatment of diabetes focuses on the attainment of an optimal glycemic control in order to impede complications.
Individuals with diabetes are more susceptible to periodontal disease, which is also recognized as the sixth complication of diabetes.28-32
The underlying pathophysiology that increases the risk of periodontal bone loss in subjects with diabetes is poorly understood; however it has been associated with the formation and accumulation of glucose-mediated advanced glycation end-products (AGEs).
AGEs accumulate in the plasma and tissues (including the periodontium) during the process of normal aging, but to an accelerated degree in subjects with diabetes.33 AGEs contribute to periodontal destruction by activating receptors called “Receptor for AGEs (RAGE)” located on the periodontium and by reducing the production of matrix proteins, such as collagen and osteocalcin by gingival and periodontal fibroblasts.34-38
It has been suggested that the pathogenesis of diabetes and its complications are associated with an increased RAGE expression.29,39
Other cell types with RAGE expression include glomerular epithelial cells (podocytes), endothelial cells, vascular smooth muscle cells, inflammatory mononuclear phagocytes and lymphocytes.39 Therefore, an impaired glycemic status may negatively affect the outcome of implant therapy. In a systematic review, Javed and Romanos19 reported that under optimal glycemia control, dental implants can osseointegrate and remain functionally stable over long durations in patients with diabetes.
Bisphosphonates (BPs), (such as alendronate, risendronate, ibandronate, and clodronate) are important group of drugs used for the treatment of metabolic and oncologic pathologies involving the skeletal system. The mode of action of BPs depends on the drugs’ chemical structure. The two main categories of BPs are the “non-nitrogen” and “nitrogen-containing” BPs.40 Non–nitrogen-containing BPs are metabolized rapidly, whereas nitrogen-containing BPs are much more potent and are not metabolized.41 These drugs act by inhibiting osteoclastic activity and inducing their apoptosis.18 BPs may be administered by either oral or intravenous routes. Oral BPs are used in the treatment of diseases such as osteoporosis and Pagets’ disease; while intravenous BPs are administered to patients with breast cancer, multiple myeloma, bone metastasis and malignant hypercalcemia. The chief complication observed in patients under either oral or intravenous BP therapy is osteonecrosis of the jaw (ONJ).42 It has been suggested that all patients under bisphosphonate therapy who are expected to receive dental implants should be informed of the possible risks of development of ONJ and consequent implant loss beforehand; and an informed-consent must be obtained prior to installation of dental implants in these individuals.14,15
Although, the risk of developing ONJ in patients using BPs is estimated to be minimal (approximately 0.09%), there still exists a controversy over the placement of dental implants in patients treated with BPs.43 Results from case-reports44-47 have shown that dental implants can osseointegrate and remain functionally stable in patients under BP therapy. Similar results have been reported in retrospective studies.48,49 Results by Bell and Bell50 showed comparable implant survival rates between patients using BPs and controls, that is, 95% and 96.5% respectively. Brooks et al.47 placed 10 implants in a patient on bisphosphonate therapy out of which, 9 implants osseointegrated successfully giving a success rate of 90%. Likewise, results from a case-report by Wang et al.44 also showed implant healing to be uneventful with no alterations in the healing process of dental implants in a patient using BPs. Fugazzotto et al.51 showed that a history of bisphosphonate therapy was not associated with the occurrence of ONJ following installation of immediately-loaded dental implants.
In their systematic review, Javed and Almas18 reported that the incidence of implant failure in patients taking BPs is minimal.
The authors also concluded that placement of dental implants in patients taking BPs can have a positive outcome.18
3.3. Osteoporosis and rheumatoid arthritis
Osteoporosis is a metabolic disease of bone characterized by low bone mineral density (BMD) and reduced bone mass due to impaired bone metabolism and imbalanced osteoblastic and osteoclastic activities.52,53 In osteoporotic bone, osteoblasts demonstrate impaired pro-liferative, synthetic and reactive ability to cellular
Underlying causes of osteoporosis include pre- and postmenopausal estrogen deficiency, excessive glucocorticoid intake, eating disorders such as anorexia nervosa and celiac disease.56,57 Although the bone quality and strength are compromised in osteoporotic patients; osteoporosis is not considered a contraindication for implant the-rapy.58,59 In a recent systematic review, Javed et al.60 assessed the effect of osteogenic coatings on the osseointegration of implants under induced osteoporotic conditions. Nearly 80% studies reported that osteogenic coatings around implant surfaces enhance bone formation, bone-to-implant contact (BIC) and bone volume (BV) under osteoporosis-like conditions. This could possibly be accredited to the increase in surface roughness of the implant caused by osteogenic coatings, which facilitate the attachment of osteoprogenitor cells to the implant surface. Holahan et al.59 conducted a retrospective study to evaluate whether a diagnosis of osteoporosis affected the survival rate of osseointegrated dental implants. In this study59, a total of 3,224 implants placed in 746 female patients aged at least 50 years old at the time of implant placement were assessed. The results showed that patients with a diagnosis of osteoporosis or osteopenia were not significantly more likely to develop implant failure compared to those without such a diagnosis.59
Krennmair et al.61 evaluated the implant treat-ment outcomes for patients suffering from autoimmune rheumatoid arthritis (RA) with or without concomitant connective tissue diseases (CTD). In this study,61 34 female patients (25 iso-lated RA; nine RA+CTD) were included. At the mean duration of follow-up of nearly 46 month, all implants presented a survival rate of 100%. In isolated RA patients, acceptable marginal bone loss (MBL) (mean: 2.1 mm; SD: 0.5 mm), pocket depth (mean: 2.8 mm; SD:3.2 mm) and healthy soft-tissue conditions (plaque/bleeding/ gingiva index Grade 0 in 80%) were observed.61 Results from a case-series report,62 showed a high implant survival rate during follow-up with a cumulative 3-year implant success rate of 96.1%. In this study, RA patients demonstrated acceptable MBL (mean: 2.1 +/- 0.5 mm) and satisfactory soft tissue conditions; whereas CTD patients showed increased MBL (mean: 3.1 +/- 0.7 mm).
The study62 concluded that a high implant and prosthodontic success rate can be anticipated in patients suffering from RA; however, the authors emphasized that optimal oral hygiene assists in ensuring stable long-term survival of dental implants in patients with RA.62
Osteoradionecrosis is usually observed several years following radiotherapy and is associated with local trauma within the hypovascular–hypocellular hypoxic tissues (that occurs as a result of radiation-induced endarteritris).63 In this regard, the interval between the end of cancer therapy and placement of dental implants may contribute to the success or failure of osseointegration. Studies64-66 have investigated the required time interval between radiotherapy and implant installation that may influence osseointegration; however the results remain debatable. In a systematic review, Zen Filho et al.67 assessed the safety of dental implants placed in irradiated bone and to discuss their viability when placed post-radiotherapy. Eight publications were assessed in this systematic review67 and the results showed a total of 331 patients received 1237 implants. The time interval between irradiation and dental implantation ranged from 6 to 15 months. The overall implant failure rate of 9.53% and osseointegration success rates ranged between 62.5% and 100%.67 In another review, Javed et al.20 assessed the implant survival rate after oral cancer therapy. In total, 21 studies were included in this review out of which, 16 studies reported that dental implants can osseointegrate and remain functionally stable in patients having undergone radiotherapy following oral cancer surgery.20 The authors concluded that dental implants can osseointegrate and remain functionally stable in patients having undergone oral cancer treatment.20
3.5. Human immunodeficiency virus infection
Human immunodeficiency virus (HIV) infection is characterized by progressive immune system failure that gives rise to the development of opportunistic infections and neoplasms. The virus invades CD4+ T lymphocytes, macrophages and dendritic cells, and the CD4+ T cell counts gradually decrease as a result of direct cytopathic action or cytotoxic CD8+T lymphocyte-mediated attack. In a recent systematic review, Ata-Ali et al.68 attempted to answer the following focused question “does HIV infection have an impact upon dental implant osseointegration?” The combinations of search terms resulted in a list of 132 titles. Consequently, 101 studies were excluded on the basis of the evaluation of the title and abstract, thereby leaving 9 articles for eligibility assessment. Amongst the studies included in this systematic review, a total of 173 dental implants were placed in 80 patients (135 implants in 56 HIV-positive individuals and 38 implants
in 24 HIV-negative patients -control groups). A single loss of dental implant osseointegration was recorded in an HIV-positive patient.68 In the study by Stevenson et al.69, 40 dental implants were placed in 20 HIV-infected patients. No implant osseointegration failures were recorded after 6 months of follow-up. Similarly, in another study of 39 dental implants placed in 24 HIV-infected patients, no implant osseointegration failures were recorded after 12 months of follow-up.70 Should dental implants placed in HIV positive patients sustain bone levels in the long-term (5 years or longer) requires further investigations.
3.6. Genetic factors
Jacobi-Gresser et al.71 assessed diagnostic markers to predict titanium implant failure.
The study reported that tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β) release on titanium stimulation were significantly higher among patients with implant failure.
The results showed that IL-1β/TNF-α release and number of risk genotypes were significantly associated with implant failure.71
Vaz et al.72 examined IL-1 gene clusters in 155 patients with 100 successful implants and 55 unsuccessful implants.
The authors concluded that successful implants were associated with a negative genetic test and that unsuccessful implants were associated with a positive genetic test.72
Casado and colleagues reported that the IL-6 genotype was 1.53 times more likely to convey peri-implant disease if the individuals had the GC genotype and allele G.
Although systemic diseases such as poorly controlled DM, RA and osteoporosis are significant risk-factors for dental implant failure, proper management of the systemic disorder and optimal oral hygiene may support osseointegration and survival of dental implants in medically-compromised patients.
Conflict of interest and financial disclosure
The author reports no conflict of interest and there was no external source of funding for the present study.
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